This study aimed to investigate the mechanisms known to regulate glucose homeostasis in human skeletal muscle of healthy and prediabetic subjects exercising in normobaric hypoxia. Seventeen healthy (H; 28.8 ± 2.4 yr; maximal oxygen consumption (V̇O2max): 45.1 ± 1.8 mL·kg-1·min-1) and 15 prediabetic (P; 44.6 ± 3.9 yr; V̇O2max: 30.8 ± 2.5 mL·kg-1·min-1) men were randomly assigned to two groups performing an acute exercise bout (heart rate corresponding to 55% V̇O2max) either in normoxic (NE) or in hypoxic (HE; fraction of inspired oxygen [Formula: see text] 14.0%) conditions. An oral glucose tolerance test (OGTT) was performed in a basal state and after an acute exercise bout. Muscle biopsies from m. vastus lateralis were taken before and after exercise. Venous blood samples were taken at regular intervals before, during, and after exercise. The two groups exercising in hypoxia had a larger area under the curve of blood glucose levels during the OGTT after exercise compared with baseline (H: +11%; P: +4%). Compared with pre-exercise, an increase in p-TBC1D1 Ser237 and in p-AMPK Thr172 was observed postexercise in P NE (+95%; +55%, respectively) and H HE (+91%; +43%, respectively). An increase in p-ACC Ser212 was measured after exercise in all groups (H NE: +228%; P NE: +252%; H HE: +252%; P HE: +208%). Our results show that an acute bout of exercise in hypoxia reduces glucose tolerance in healthy and prediabetic subjects. At a molecular level, some adaptations regulating glucose transport in muscle were found in all groups without associations with glucose tolerance after exercise. The results suggest that hypoxia negatively affects glucose tolerance postexercise through unidentified mechanisms.NEW & NOTEWORTHY The molecular mechanisms involved in glucose tolerance after acute exercise in hypoxia have not yet been elucidated in human. Due to the reversible character of their status, prediabetic individuals are of particular interest for preventing the development of type 2 diabetes. The present study is the first to investigate muscle molecular mechanisms during exercise and glucose metabolism after exercise in prediabetic and healthy subjects exercising in normoxia and normobaric hypoxia.
Keywords: AMPK; GLUT4; OGTT; cycling; diabetes.